POS0735 EFFECT OF OSTEOPOROSIS ON MAJOR ADVERSE CARDIOVASCULAR EVENTS (MACES) AND MORTALITY IN SYSTEMIC LUPUS ERYTHEMATOSUS: A LONGITUDINAL STUDY
Authors: C. C. Mok, K. L. Chan, L. Y. Ho, C. H. To
Journal: Annals of the Rheumatic Diseases (2022)

Objectives To study the effect of osteoporosis on major adverse cardiovascular events (MACEs) and mortality in a longitudinal cohort of patients with systemic lupus erythematosus (SLE). Methods Patients who fulfilled ≥4 1997 ACR criteria for SLE and participated in a cross-sectional study on osteoporosis in the year 2011 were studied. All patients had a dual energy x-ray absorptiometry (DXA) scan (Delphi densitometer; Hologic, Bedford, USA) performed between the years 2004-2008 and were followed in the rheumatology clinics by the same team of physicians. The incidence of new MACEs, which were defined as ischemic vascular events (acute coronary syndrome, stroke, peripheral vascular disease) documented by imaging and angiographic studies, was evaluated. Patients were stratified into 2 groups according to the presence of osteoporosis at baseline, which was defined as a DXA T score of &lt;-2.5 or Z score &lt;-2.0 at the hip, femoral neck or lumbar spine, or having a past history of fragility fractures. The effect of osteoporosis on the development of MACEs and mortality was studied by Cox regression analysis, adjusted for demographic characteristics, traditional cardiovascular risk factors, antiphospholipid antibodies and the use of medications. Results 383 SLE patients were studied (age at DXA scan 40.5±13 years; 94% women; SLE duration 8.0±7.4 years). Osteoporosis at the hip, femoral neck or spine at baseline was present in 105 patients (13 with old fragility fractures) and 8 patients had osteopenia and past fragility fractures. The demographic characteristics, prevalence of traditional atherosclerotic risk factors and antiphospholipid (aPL) antibodies (lupus anticoagulant or moderate/high titers of IgG-anticardiolipin antibodies) were not significantly different between those with osteoporosis/fracture (N=113) and without (N=270). Patients with osteoporosis/fracture were more likely to be using glucocorticoids (79% vs 62%; p=0.002) and mycophenolate mofetil/azathioprine/calcineurin inhibitors (58% vs 48%; p=0.08) but less likely to be treated with hydroxychloroquine (40% vs 51%; p=0.051) at baseline. Over a follow-up of 153±41 months, 44 new MACEs (acute coronary syndrome [n=19]; ischemic stroke [n=19]; peripheral vascular disease with digital gangrene/amputation [n=6]) developed in 42 patients. The incidence of MACEs was significantly higher in patients with osteoporosis/fracture than those without (1.59 vs 0.63/100 patient-years; p=0.001). The cumulative risk of MACEs at 3, 5 and 10 years was 6.3%, 11.7%, 14.7%, and 0.4%, 1.9%, 4.7%, respectively, in the osteoporosis and non-osteoporosis groups (log rank test; p=0.002; univariate hazard ratio 2.58[1.40-4.74]; p=0.002). In a Cox regression model, osteoporosis/fracture remained an independent risk factor for the development of MACEs after adjustment for age, sex, LDL level, atherogenic index, diabetes mellitus, hypertension, past MACE, aPL antibodies, smoking, obesity and the use medications that included immunosuppressive drugs, aspirin/warfarin, statins, vitamin D and bisphosphonates (HR 2.41[1.25-4.67]; p=0.009). At last follow-up, 62(16%) patients succumbed (MACEs in 8 patients [vascular mortality], infective complications in 27 patients, cancer in 10 patients). Osteoporosis/fracture was associated with vascular mortality (HR 11.1[1.02-120]; p=0.048) but not with all-cause mortality (HR 1.55[0.89-2.68]; p=0.12) after adjustment for the same covariates in separate multivariate models. Conclusion Osteoporosis increases the risk of MACEs and vascular mortality in patients with SLE, which is not accounted by traditional vascular risk factors. Elevation of inflammatory cytokines in SLE that are common to bone metabolism and atherosclerotic vascular disease may be responsible. Disclosure of Interests None declared